Network pharmacology and molecular docking-based investigation on the mechanism of BPA in depression and experimental verification in offspring mice.

BACKGROUND: Bisphenol A (BPA) is an environmental endocrine disruptor that may contribute to depression. However, its molecular mechanism requires further elucidation. METHOD: Data from NHANES 2005-2010 were analyzed to evaluate the correlation between BPA and depression. Network pharmacology was used to search for potential targets, molecular docking was used to appraise the interaction between the BPA and related targets, and a model of depression-like behaviors in offspring mice as well as the following behavioral and molecular biology tests were used to verify the above results. RESULTS: Survey-weighted linear regression, adjusting for age, sex, and race/ethnicity, suggested that higher urinary BPA concentrations were positively associated with depression scores. Network pharmacology identified multiple depression-related genes that may be targeted by BPA, and protein-protein interaction analysis highlighted hub genes involved in inflammatory pathways. Molecular docking provided preliminary computational predictions of binding affinities between BPA and key targets, including PTGS2, suggesting possible interactions that warrant further experimental validation. In the experiment with offspring mice, BPA enhanced PTGS2 level, increased PGE2 production and EP2 expression downstream, amplified inflammatory response, and eventually led to depression-like behaviors. CONCLUSION: BPA exposure may contribute to depression-like behaviors, potentially through PTGS2-mediated neuroinflammation.